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The aim of this study was to evaluate the safety of drinking carbohydrate-containing fluids two hours prior to surgery in older adults using ultrasonography.We conducted a nonrandomized and noninferiority comparative study in 60 patients aged over 65 yr who were scheduled for total knee arthroplasty. Patients who were fasted from midnight (fasting group) or who drank 400 mL of a carbohydrate-containing fluid (carbohydrate ingestion group) two hours prior to surgery were matched for age, sex, and body mass index. We measured the cross-sectional area (CSA) of gastric antrum using ultrasound and estimated the gastric fluid volume as the study's primary outcome measure. The noninferiority margin (δ) for the mean difference was predefined as 50 mL. The secondary outcome measures included CSA of the antrum and qualitative gastric volume.The mean (standard deviation) gastric volume was not significantly different between the fasting group and the carbohydrate ingestion group (30.2 [25.4] mL vs 28.4 [35.8] mL; each group, n = 30; P = 0.81). The mean difference in gastric volume was -1.9 mL (95% confidence interval [CI], -17.9 to 14.2), and the upper limit of the 95% CI was lower than the prespecified noninferiority limit (δ = 50 mL). Secondary outcomes were not significantly different between the two groups.Drinking of carbohydrate-containing fluid two hours prior to surgery was noninferior to overnight fasting with respect to residual gastric volume at induction of anesthesia in healthy older adults who undergoing total knee arthroplasty.ClinicalTrials.gov (NCT04514380); registered 14 August 2020.RéSUMé: OBJECTIF: L’objectif de cette étude était d’évaluer l’innocuité de la consommation d’une préparation glucidique deux heures avant une chirurgie chez les personnes âgées à l’aide de l’échographie. MéTHODE: Nous avons mené une étude comparative non randomisée et de non-infériorité chez 60 patients âgés de plus de 65 ans qui devaient bénéficier d’une arthroplastie totale du genou. Les patients étaient à jeun depuis minuit (groupe à jeun) ou avaient bu 400 mL d’une préparation glucidique (groupe d’ingestion de glucides) deux heures avant la chirurgie et ont été appariés pour l’âge, le sexe et l’indice de masse corporelle. Nous avons mesuré la section transversale de l’antre gastrique à l’aide de l’échographie et estimé le volume de liquide gastrique en tant que mesure du critère d’évaluation principal de l’étude. La marge de non-infériorité (δ) pour la différence moyenne a été prédéfinie à 50 mL. Les mesures de critères d’évaluation secondaires comprenaient la section transversale de l’antre et le volume gastrique qualitatif. RéSULTATS: Le volume gastrique moyen (écart type) n’était pas significativement différent entre le groupe à jeun et le groupe d’ingestion de glucides (30,2 [25,4] mL vs 28,4 [35,8] mL; chaque groupe, n = 30; P = 0,81). La différence moyenne de volume gastrique était de -1,9 mL (intervalle de confiance [IC] à 95 %, -17,9 à 14,2), et la limite supérieure de l’IC 95 % était inférieure à la limite de non-infériorité prédéfinie (δ = 50 mL). Aucune différence intergroupe significative n’a été observée dans les critères d’évaluation secondaires. CONCLUSION: La consommation d'une préparation glucidique deux heures avant la chirurgie n'était pas inférieure au jeûne nocturne en ce qui concerne le volume gastrique résiduel à l'induction de l'anesthésie chez les personnes âgées en bonne santé qui bénéficient d'une arthroplastie totale du genou. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04514380); enregistrée le 14 août 2020.

Background: When an imbalance occurs between the demand and capacity for protein folding, unfolded proteins accumulate in the endoplasmic reticulum (ER) lumen and activate the unfolded protein response (UPR). In addition, unfolded proteins are cleared from the ER lumen for ubiquitination and subsequent cytosolic proteasomal degradation, which is termed as the ER-associated degradation (ERAD) pathway. This study focused on changes in the UPR and ERAD pathways induced by the repeated inhalation anesthetic exposure in Caenorhabditis elegans. Methods: Depending on repeated isoflurane exposure, C. elegans was classified into the control or isoflurane group. To evaluate the expression of a specific gene, RNA was extracted from adult worms in each group and real-time polymerase chain reaction was performed. Ubiquitinated protein levels were measured using western blotting, and behavioral changes were evaluated by chemotaxis assay using various mutant strains. Results: Isoflurane upregulated the expression of ire-1 and pek-1 whereas the expression of atf-6 was unaffected. The expression of both sel-1 and sel-11 was decreased by isoflurane exposure, possibly indicating the inhibition of retro-translocation. The expression of cdc-48.1 and cdc-48.2 was decreased and higher ubiquitinated protein levels were observed in the isoflurane group than in the control, suggesting that deubiquitination and degradation of misfolded proteins were interrupted. The chemotaxis indices of ire-1, pek-1, sel-1, and sel-11 mutants decreased significantly compared to N2, and they were not suppressed further even after the repeated isoflurane exposure. Conclusion: Repeated isoflurane exposure caused significant ER stress in C. elegans. Following the increase in UPR, the ERAD pathway was disrupted by repeated isoflurane exposure and ubiquitinated proteins was accumulated subsequently. UPR and ERAD pathways are potential modifiable neuroprotection targets against anesthesia-induced neurotoxicity.

Background This study was performed to evaluate the effectiveness of ramosetron orally disintegrating tablets (ODTs) in preventing post-discharge nausea and/or vomiting (PDNV) in female patients following outpatient surgery under general anesthesia. Methods This multicenter randomized study included three South Korean tertiary hospitals. Before surgery, 138 patients were randomly allocated into two groups. In the ramosetron group, ramosetron ODT 0.1 mg was administered after discharge in the morning of postoperative days 1 and 2. Metoclopramide 10 mg was administered as a rescue antiemetic (capped at 30 mg per day). In the control group, patients were administered only metoclopramide 10 mg when nausea and/or vomiting occurred. The primary outcome was the incidence of nausea during 24 h after discharge. Results We found significant differences in the incidence (13% vs. 33%, P = 0.008) and severity (P = 0.011) of nausea between the ramosetron and the control groups during 24 h after discharge. In addition, the rate of rescue antiemetic (metoclopramide) administration during 24 h after discharge was lower in the ramosetron group (6%) than in the control group (18%) (P = 0.033). Patient satisfaction score was higher in the ramosetron group than in the control group (P < 0.001). Conclusion Ramosetron ODT reduces the incidence and severity of postoperative nausea after discharge during the first 24 h and may be a valuable option for the prevention of PDNV in female patients after day surgery under general anesthesia. Trial registration ClinicalTrials.gov, NCT04297293. Registered on 05 March 2020

This meta-analysis aimed to determine whether peripheral nerve blocks (PNB) reduce postoperative delirium (POD) in elderly patients undergoing hip surgery. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022328320). The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for randomized controlled trials (RCTs) on 26 April 2022. A total of 19 RCTs with 1977 participants were included. Perioperative PNB lowered the POD incidence on the third postoperative day (OR: 0.59, 95% CI [0.40 to 0.87], p = 0.007, I2 = 35%), in patients without underlying cognitive impairment (OR: 0.47, 95% CI [0.30 to 0.74], p = 0.001, I2 = 30%), and when a fascia iliaca compartment block (OR: 0.58, 95% CI [0.37 to 0.91], p = 0.02, I2 = 0%) or a femoral nerve block (OR: 0.33, 95% CI [0.11 to 0.99], p = 0.05, I2 = 66%) were performed. The pain score was also reduced (SMD: −0.83, 95% CI [−1.36 to −0.30], p = 0.002, I2 = 95%) after PNB. Perioperative PNB can lower the POD incidence and pain scores up to the third postoperative day. However, considering the wide variety of PNBs performed, more trials are needed to identify the effects of each PNB on POD.

Background and objectivesData is insufficient to determine whether perioperative statin use increases or decreases postoperative pain. This study aimed to investigate the association between perioperative statin use and pain outcomes after total knee arthroplasty performed under spinal anesthesia.MethodsThis is a retrospective, observational study based on medical records from a tertiary hospital between January 2005 and October 2017. Medical records of patients who underwent elective total knee arthroplasty under spinal anesthesia as inpatients were analyzed. Pain outcomes were compared through postoperative day (POD) 3 in patients who were taking statins perioperatively versus patients who were not taking statins.ResultsA total of 1088 propensity-matched participants were included in the final analysis (544 patients in the statin group and 544 patients in the non-statin group). The total morphine equivalent consumption through POD 3 was higher in the statin group than in the non-statin group (mean (SD), statin group: 525.4 (119.7) vs non-statin group: 495.3 (115.3), 95% CI of the difference: 15.9 to 44.4, pConclusionsPerioperative statin use is associated with a significant increase in postoperative opioid consumption after total knee arthroplasty performed under spinal anesthesia; however, this increase was so marginal that its clinical importance remains controversial.

Neurotoxic effects of local anesthetics (LAs) on developing motor neurons have not been documented. We investigated the neurotoxic effects of LAs on developing motor neurons in terms of cell viability, cytotoxicity, reactive oxygen species (ROS), and apoptosis. Embryonic spinal cord motor neurons were isolated from Sprague-Dawley rat fetuses and exposed to one of the three LAs—lidocaine, bupivacaine, or ropivacaine—at concentrations of 1, 10, 100, or 1000 µM. The exposure duration was set to 1 or 24 h. The neurotoxic effects of LAs were determined by evaluating the following: cell viability, cytotoxicity, ROS production, and apoptosis. In the 1-h exposure group, the motor neurons exposed to lidocaine and bupivacaine had reduced cell viability and increased cytotoxicity, ROS, and apoptosis in a concentration-dependent manner. Lidocaine showed the highest toxicity, followed by bupivacaine. In the 24-h exposure group, all three LAs showed significant effects (decreased cell viability and increased cytotoxicity, ROS, and apoptosis) on the motor neurons in a concentration-dependent manner. The neurotoxic effects of lidocaine were greater than those of bupivacaine and ropivacaine. Ropivacaine appeared to have the least effect on motor neurons. This study identified the neurotoxic effects of lidocaine and bupivacaine on developing spinal cord motor neurons.

Spinal cord ischemia is one of the most serious complications of aortic repair in patients with acute aortic syndrome. However, the effect of hypotension before aortic clamping on spinal cord injury has not been documented. A total of 48 male Sprague-Dawley rats were randomly divided into four groups: the sham group, control group (mean arterial pressure (MAP) &lt, 90% of baseline value before aortic clamping), mild hypotension group (MAP &lt, 80%), and profound hypotension group (MAP &lt, 60%). Spinal cord ischemia was induced using a balloon-tipped catheter placed in the descending thoracic aorta. Neurological function of the hind limbs was evaluated for seven days after reperfusion and recorded using a motor deficit index (MDI). The spinal cord was then harvested for histopathological examination and evaluation of oxidative stress and inflammation. The profound hypotension group demonstrated a significantly higher MDI 48 h post-reperfusion and lower number of normal motor neurons than the other groups (p &lt, 0.001). The levels of tissue malondialdehyde and tumor necrosis factor-&alpha, (TNF-&alpha, ) were also significantly increased in the profound hypotension group compared with other groups. Profound hypotension before aortic clamping can aggravate neurologic outcomes after aortic surgery by exacerbating neurologic injury and reducing the number of normal motor neurons.

Ultrasound-guided erector spinae plane block (ESPB), a recent regional analgesic technique, has been used to manage acute pain after surgery. The aim of this meta-analysis is to identify the benefits of ESPB in patients undergoing laparoscopic cholecystectomy (LC). The authors searched PubMed, EMBASE, CENTRAL, CINAHL, and Web of Science to identify all randomized controlled trials (RCTs) evaluating the effects of ESPB on postoperative pain after LC. Primary outcome was defined as 24 h cumulative opioid consumption. Secondary outcomes were pain scores and the incidence of postoperative nausea and vomiting (PONV). We estimated mean differences (MD) and odds ratio (OR) using a random-effects model. A total of 8 RCTs, including 442 patients, were included in the final analysis. Postoperative opioid consumption was significantly lower in the ESPB group than in the control group (MD &minus, 4.72, 95% CI &minus, 6.00 to &minus, 3.44, p &lt, 0.001). Compared with the control group, the ESPB group also showed significantly lower pain scores and incidence of PONV. A separate analysis of RCTs comparing ESPB with oblique subcostal transversus abdominis plane (OSTAP) block showed that the analgesic efficacy of ESPB was similar to that of OSTAP block. The results of this meta-analysis demonstrated that ESPB may provide effective postoperative analgesia in patients undergoing LC.

Background: Tranexamic acid (TXA) is the most widely used hemostatic agent in surgical patients. However, when used in a high dose, it could cause a seizure in the postoperative period. The exact effector mechanism behind the seizure triggering remains unknown. Therefore, the authors investigated the effects of TXA on the activity of glutamate transporter type 3 (excitatory amino acid transporter 3; EAAT3), which is the main neuronal glutamate transporter type. Methods: EAAT3 was expressed in Xenopus laevis oocytes through mRNA injection. Oocytes were incubated with diluted tranexamic acid for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 M L-glutamate. Responses were quantified by integrating the current traces and reported in microcoulombs (C). Results were presented as mean  SEM.Results: TXA (30 to 1,000 M) significantly decreased EAAT3 activity. Our kinetic study showed that Vmax was significantly decreased in the TXA group compared with the control group (1.1  0.1 vs. 1.4  0.1 C, n = 18–23, P = 0.043), but the Km did not significantly change (12.7  3.9 M for TXA vs. 12.8  3.8 for control, n = 18–23, P = 0.986).Conclusions: Our results suggest that TXA attenuates EAAT3 activity, which may explain its proconvulsant effect.

Postoperative delirium (PD) remains an issue in cardiac surgery despite the constant efforts to reduce its incidence. In this retrospective study, the incidence of PD was evaluated in patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) according to different primary anesthetic agents: sevoflurane and dexmedetomidine- versus propofol-based anesthesia. A total of 534 patients who underwent heart-valve surgery or coronary artery bypass graft surgery with CPB between January 2012 and August 2017 were divided into 2 groups according to the main anesthetic agent: sevoflurane with dexmedetomidine (sevo-dex group, n = 340) and propofol (propofol group, n = 194). The incidence of PD was evaluated as the primary outcome. Patient-, surgery-, and anesthesia-related factors and postoperative complications were investigated as secondary outcomes. To reduce the risk of confounding effects between the 2 groups, 194 patients were selected from the sevo-dex group after propensity-score matching. After propensity-score matching, the incidence of PD was not significantly different between the sevo-dex (6.2%) and propofol (10.8%) groups (P = .136). In comparisons of the incidence of each type of PD, only hyperactive PD occurred significantly less frequently in the sevo-dex group (P = .021). Older age, lower preoperative albumin levels, and emergency surgery were significant risk factors for PD. The overall incidence of PD after cardiac surgery with CPB did not differ between patients receiving sevoflurane and dexmedetomidine-based versus propofol-based anesthesia. Only hyperactive PD occurred less frequently in patients receiving sevoflurane and dexmedetomidine-based anesthesia.

To generate a biobetter that has improved therapeutic activity, we constructed scFv libraries via random mutagenesis of several residues of CDR-H3 and -L3 of hu4D5. The scFv clones were isolated from the phage display libraries by stringent panning, and their anti-proliferative activity against HER2-positive cancer cells was evaluated as a primary selection criterion. Consequently, we selected AH06 as a biobetter antibody that had a 7.2-fold increase in anti-proliferative activity (IC50: 0.81 nM) against the gastric cancer cell line NCI-N87 and a 7.4-fold increase in binding affinity (KD: 60 pM) to HER2 compared to hu4D5. The binding energy calculation and molecular modeling suggest that the substitution of residues of CDR-H3 to W98, F100c, A101 and L102 could stabilize binding of the antibody to HER2 and there could be direct hydrophobic interactions between the aromatic ring of W98 and the aliphatic group of I613 within HER2 domain IV as well as the heavy and light chain hydrophobic interactions by residues F100c, A101 and L102 of CDR-H3. Therefore, we speculate that two such interactions were exerted by the residues W98 and F100c. A101 and L102 may have a synergistic effect on the increase in the binding affinity to HER2. AH06 specifically binds to domain IV of HER2, and it decreased the phosphorylation level of HER2 and AKT. Above all, it highly increased the overall level of p27 compared to hu4D5 in the gastric cancer cell line NCI-N82, suggesting that AH06 could potentially be a more efficient therapeutic agent than hu4D5.

The use of lidocaine in spinal anesthesia may increase the risk of transient neurological symptoms (TNS) according to previous meta-analyses. However, the previous meta-analyses lacked data on some other local anesthetics and thus, more evaluations are still needed to compare the effect of lidocaine on the development of TNS. The objective of this study was to compare the risk of TNS according to lidocaine versus other local anesthetics in patients undergoing spinal anesthesia. A total of 39 randomized controlled trials with 4733 patients were analyzed. The incidence of TNS was 10.8% in the lidocaine group and was 2.2% in the control groups (risk ratio (RR) 4.12, 95% confidence interval (CI) 3.13 to 5.43, p &lt, 0.001). In subgroup analysis, lidocaine increased the incidence of TNS compared with other local anesthetics except mepivacaine, ropivacaine or sameridine. The risk of TNS was higher in the hyperbaric (p &lt, 0.001) or isobaric lidocaine (p &lt, 0.001) group compared with the control group, but there were no differences found between the two groups when hypobaric lidocaine was administered (p = 1.00). This study confirmed that lidocaine for spinal anesthesia still causes TNS more frequently than most other local anesthetics, especially when hyperbaric or isobaric lidocaine was used.

In this work, we wanted to develop a probiotic from famous longevity villages in Korea. We visited eight longevity villages in Korea to collect fecal samples from healthy adults who were aged above 80 years and had regular bowel movements, and isolated lactic-acid-producing bacteria from the samples. Isolated colonies that appeared on MRS agar containing bromophenol blue were identified by means of 16S rRNA sequencing, and 102 of the isolates were identified as lactic-acid-producing bacteria (18 species). Lactobacillus fermentum was the most frequently found species. Eight isolates were selected on the basis of their ability to inhibit the growth of six intestinal pathogens (Escherichia coli O157:H7, Salmonella enterica subsp. enterica Typhimurium, Salmonella enterica subsp. enterica Enteritidis, Enterococcus faecalis, Staphylococcus aureus, and Listeria monocytogenes) and their susceptibility to 15 antimicrobial agents. Among these eight isolates, four Lactobacillus fermentum isolates were found not to produce any harmful enzymes or metabolites. Among them, Lactobacillus fermentum isolate no. 24 showed the strongest binding to intestinal epithelial cells, the highest immune-enhancing activity, anti-inflammation activity, and anti-oxidation activity as well as the highest survival rates in the presence of artificial gastric juice and bile solution. This isolate, designated Lactobacillus fermentum PL9988, has all the characteristics for a good probiotic.

Background: The use of sedatives (propofol or dexmedetomidine) is common in total knee arthroplasty (TKA) or total hip arthroplasty (THA) under spinal anesthesia. Although propofol and dexmedetomidine have been reported to decrease the risk of acute kidney injury (AKI) after cardiac surgery, their effects on AKI incidence after TKA or THA are still unknown. The purpose of this study was to investigate the associations between sedative dosage (propofol and dexmedetomidine) and AKI incidence after TKA or THA under spinal anesthesia. Methods: This retrospective observational study analyzed medical records of adult patients aged 18 years or older who underwent unilateral TKA or THA under spinal anesthesia at a single tertiary care hospital between January 2007 and June 2018. Data were analyzed using univariable and multivariable logistic regression analyses. Results: A total of 5,663 patients were included in the analysis (TKA: 3,570, 63.0%; THA: 2,093, 37.0%), and 147 patients (2.6%) developed AKI in postoperative days 0–3. Multivariable logistic regression analysis showed that propofol dosage (odds ratio: 0.99, 95% confidence interval: 0.94, 1.05; P=0.839) and dexmedetomidine dosage (odds ratio: 0.95, 95% confidence interval: 0.84, 1.09; P=0.461) were not significantly associated with AKI incidence. Conclusions: This study demonstrated no significant association between sedative uses (propofol, dexmedetomidine) and AKI incidence after THA or TKA under spinal anesthesia, and use of such sedatives does not require extreme caution.

We performed a study to investigate whether contamination of hemostasis samples with a glucose-containing solution might generate spurious results in rotational thromboelastometry (ROTEM) tests. Venous blood was taken from 12 healthy volunteers and divided into 4 specimen bottles, which were contaminated with different concentrations (0%, 5%, 10%, and 20%) of glucose solution. Significant lengthening of INTEMCT was observed in the 10% and 20% groups compared with baseline values (7.7% and 9%, P = 0.041 and P = 0.037, respectively). INTEMCFT increased by 20.1% in the 20% group (P = 0.005). INTEMα-angle and INTEMMCF decreased by 3.9% and 2.7%, respectively, in the 20% group (P = 0.010 and P = 0.049, respectively). EXTEMCFT was prolonged significantly, by 10.2%, 15.5%, and 25.6%, in the 5%, 10%, and 20% groups, respectively (P = 0.004, P

The adverse effects of spinal anesthesia (SA) include arterial hypotension and bradycardia. The aim of this study was to compare the effects of 2 type 3 serotonin receptor antagonists in SA-induced adverse effects. Specifically, we assessed whether ramosetron was more effective than ondansetron in reducing SA-induced decreases in blood pressure (BP) and heart rate (HR).A total of 117 patients undergoing orthopedic surgery and receiving SA were intravenously administered 0.3 mg of ramosetron (n = 39, group R), 4 mg of ondansetron (n = 39, group O4), or 8 mg of ondansetron (n = 39, group O8). Systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), HR, and the lowest SBP, DBP, MBP, and HR values were measured preoperatively (baseline) and intraoperatively. The incidence of postoperative nausea and vomiting, the need for rescue antiemetics, the amount of patient-controlled analgesia consumption, and pain score in the first 48 hours after surgery were determined.Baseline values did not significantly differ among the 3 groups. After SA, SBP, DBP, MBP, and HR were lower than their baseline values in all 3 groups. The differences between the baseline and the lowest values were significantly less in group R than in groups O4 and O8 with respect to SBP (P0.001), DBP (P = 0.001), and MBP (P0.001) less in group R than in group O4 with respect to HR (P = 0.032). Intergroup differences were not significant for postoperative nausea and vomiting, the need for rescue antiemetics, patient-controlled analgesia consumption, or pain score.The administration of ramosetron (0.3 mg) significantly attenuated the SA-induced decrease in BP compared with 4 or 8 mg of ondansetron and HR compared with 4 mg of ondansetron.

(−)-A26771B, a novel 16-membered macrolide with antibiotic activity, has been formally synthesized. In the synthesis ruthenium catalyzed ring-closing olefin metathesis (RCM) was used as a key reaction to construct the lactone ring.